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Mashup Score: 30Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle - 3 hour(s) ago
Highly pathogenic avian influenza (HPAI) viruses cross species barriers and have the potential to cause pandemics. In North America, HPAI A(H5N1) viruses related to the goose/Guangdong 2.3.4.4b hemagglutinin phylogenetic clade have infected wild birds, poultry, and mammals. Our genomic analysis and epidemiological investigation showed that a reassortment event in wild bird populations preceded a single wild bird-to-cattle transmission episode. The movement of asymptomatic cattle has likely played a role in the spread of HPAI within the United States dairy herd. Some molecular markers in virus populations were detected at low frequency that may lead to changes in transmission efficiency and phenotype after evolution in dairy cattle. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for infection and subsequent spread of the virus to human populations. ### Competing Interest Statement The authors have declared no competing interest.
Source: www.biorxiv.orgCategories: General Medicine News, Infectious DiseaseTweet
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Mashup Score: 1
While electroencephalography (EEG) and magnetoencephalography (MEG) are well-established non-invasive methods in neuroscience and clinical medicine, they suffer from low spatial resolution. Particularly challenging is the accurate localization of subcortical sources of M/EEG, which remains a subject of debate. To address this issue, we propose a four-layered convolutional neural network (4LCNN) designed to precisely locate both cortical and subcortical source activity underlying M/EEG signals. The 4LCNN was trained using a vast dataset generated by forward M/EEG simulations based on a realistic head volume conductor model. The 4LCNN implicitly learns the characteristics of M/EEG and their sources from the training data without need for explicitly formulating and fine-tuning optimal priors, a common challenge in conventional M/EEG source imaging techniques. We evaluated the efficacy of the 4LCNN model on a validation dataset comprising forward M/EEG simulations and two types of real exp
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 0Human striatal progenitor cells that contain inducible safeguards and overexpress BDNF rescue Huntington's disease phenotypes in R6/2 mice - 15 hour(s) ago
Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disorder characterized by striatal atrophy. Reduced trophic support due to decreased striatal levels of neurotrophins (NTs), mainly brain-derived neurotrophic factor (BDNF), contributes importantly to HD pathogenesis; restoring NTs has significant therapeutic potential. Human pluripotent stem cells (hPSC) offer a scalable platform for NT delivery but has potential safety risks including teratoma formation. We engineered hPSCs to constitutively produce BDNF and contain inducible safeguards to eliminate these cells if safety concerns arise. This study examined the efficacy of intrastriatally transplanted striatal progenitor cells (STRpcs) derived from these hPSCs against HD phenotypes in R6/2 mice. Engrafted STRpcs overexpressing BDNF alleviated motor and cognitive deficits and reduced mutant huntingtin aggregates. Activating the inducible safety switch with rapamycin safely eliminated the engrafted cells. These results
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 0Lateral Prefrontal Theta Oscillations Causally Drive a Computational Mechanism Underlying Conflict Expectation and Adaptation - 15 hour(s) ago
Adapting our behavior to environmental demands relies on our capacity to perceive and manage potential conflicts within our surroundings. While evidence implicates the involvement of the lateral prefrontal cortex and theta oscillations in detecting conflict stimuli, their roles in conflict expectation remain elusive. Consequently, the exact computations and neural mechanisms underlying these cognitive processes still need to be determined. To address this gap, we employed an integrative approach involving cognitive computational modeling, fMRI, TMS, and EEG. Our results revealed a computational process underlying conflict expectation, which correlated with activity in the superior frontal gyrus (SFG). Furthermore, rhythmic TMS in the theta range applied over the SFG, but not over the inferior frontal junction, induced endogenous theta activity, enhancing computations associated with conflict expectation. These findings provide compelling evidence for the causal involvement of SFG theta
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 0Identification of Fibrinogen as a Plasma Protein Binding Partner for Lecanemab Biosimilar IgG: Implications for Alzheimer's Disease Therapy - 15 hour(s) ago
Objective: Recombinant monoclonal therapeutic antibodies like lecanemab, which target amyloid beta in Alzheimer’s disease, offer a promising approach for modifying the disease progression. Due to its relatively short half-life, Lecanemab, administered as a bi-monthly infusion (typically 10mg/kg) has a relatively brief half-life. Interaction with abundant plasma proteins binder in the bloodstream can affect pharmacokinetics of drugs, including their half-life. In this study we investigated potential plasma protein binding interaction to lecanemab using lecanemab biosimilar. Methods: Lecanemab biosimilar used in this study was based on publicly available sequences. ELISA and Western blotting were used to assess lecanemab biosimilar immunoreactivity in the fractions human plasma sample obtained through size exclusion chromatography. The binding of lecanemab biosimilar to candidate binders was confirmed by Western blotting, ELISA, and surface plasmon resonance analysis. Results: Using a co
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 0Reduction of Neuroinflammation and Seizures in a Mouse Model of CLN1 Batten Disease using the Small Molecule Enzyme Mimetic, N-Tert-Butyl Hydroxylamine. - 15 hour(s) ago
Infantile neuronal ceroid lipofuscinosis (CLN1 Batten Disease) is a devastating pediatric lysosomal storage disease caused by pathogenic variants in the CLN1 gene, which encodes the depalmitoylation enzyme, palmitoyl-protein thioesterase 1 (PPT1). CLN1 patients present with visual deterioration, psychomotor dysfunction, and recurrent seizures until neurodegeneration results in death, typically before fifteen years of age. Histopathological features of CLN1 include aggregation of lysosomal autofluorescent storage material (AFSM), as well as profound gliosis. The current management of CLN1 is relegated to palliative care. Here, we examine the therapeutic potential of a small molecule PPT1 mimetic, N-tert-butyl hydroxylamine (NtBuHA), in a Cln1-/- mouse model. Treatment with NtBuHA reduced AFSM accumulation both in vitro and in vivo. Importantly, NtBuHA treatment in Cln1-/- mice reduced neuroinflammation, mitigated epileptic episodes, and normalized motor function. Live cell imaging of Cl
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 0Divergent short-term plasticity creates parallel pathways for computation and behavior in an olfactory circuit - 15 hour(s) ago
To enable diverse sensory processing and behavior, central circuits use divergent connectivity to create parallel pathways. However, linking subcellular mechanisms to the circuit-level segregation of computation has been challenging. Here, we investigate the generation of parallel processing within a divergent network in the Drosophila olfactory system, where single projection neurons target multiple types of lateral horn neuron (LHN). One LHN type generates sustained responses and adapts divisively to encode temporal odor contrast. The other generates transient responses and adapts subtractively to encode a form of positive temporal prediction error. These coding differences originate from subcellular differences in short-term plasticity in projection neuron axons. Prediction error arises from strongly facilitating synapses, which depend on the presynaptic priming factor Unc13B. The temporal contrast code arises from mildly depressing synapses that engage additional gain control imple
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 0Early life growth and cellular heterogeneity in the short-lived African turquoise killifish telencephalon - 15 hour(s) ago
The African turquoise killifish (Nothobranchius furzeri) is becoming a favorable model for neurobiological research. The combination of a short lifespan and a declining neuroregenerative capacity upon aging makes the killifish ideally suited for research on brain aging and regeneration. A remarkable cellular diversity makes up the young-adult killifish telencephalon, characterized by highly proliferative non-glial progenitors and four spatially distinct radial glia subtypes. In contrast to a relatively slow embryonic development, hatching is followed by a period of accelerated growth in the short-lived N. furzeri strain; GRZ. Accordingly, the brain of this teleost experiences a period of rapid expansion and maturation. In this study, we charted the growth progression of the killifish telencephalon during early post-embryonic development. We identified a dynamic cellular buildup of the neurogenic niches sustaining this explosive growth. Spatial data revealed specific differences between
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 3Neuronal downregulation of PLCG2 impairs synaptic function and elicits Alzheimer disease hallmarks - 15 hour(s) ago
We developed a high content screening to investigate how Alzheimer disease (AD) genetic risk factors may impair synaptic function in rat primary neuronal cultures. Out of the gene targets identified, we found that shRNA-mediated downregulation of Plcg2 in mouse dentate gyrus neurons consistently impaired dendritic morphology and synaptic function. In human neuronal cultures (hNCs), PLCG2 downregulation also impaired synaptic function and was associated with increased levels of Abeta; and TAU phosphorylation, potentially via the AKT/GSK3beta axis. Very rare PLCG2 loss-of-function (LoF) variants were associated with a 10-fold increased AD risk and LoF carriers exhibit low mRNA/protein PLCG2 levels, consistent with nonsense-mediated mRNA decay mechanisms. Restoring PLCG2 levels in shPLCG2-hNCs fully reversed the disease-related phenotypes. Our findings indicate that the downregulation of PLCG2 increases the risk of AD by impairing synaptic function and increasing the levels of Abeta and T
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 0Sex specific effects of dorsomedial striatal cannabinoid receptor-1 signaling on Pavlovian outcome devaluation. - 15 hour(s) ago
Cannabinoid-1 receptor (CB1R) signaling in the dorsal striatum regulates the shift from flexible to habitual behavior in instrumental outcome devaluation. Based on prior work establishing individual, sex, and experience-dependent differences in Pavlovian behaviors, we predicted a role for dorsomedial striatum CB1R signaling in driving sign-tracking and rigid responding in Pavlovian outcome devaluation. We trained male and female rats in Pavlovian Lever Autoshaping to determine sign-, or goal- or intermediate tracking groups. After extended Pavlovian training, we gave intra-DMS infusions of the CB1R inverse agonist, rimonabant, before satiety-induced outcome devaluation test sessions, in which we sated rats on training pellets (devalued) or home cage chow (valued) and examined responding to cues in brief nonreinforced Pavlovian Lever Autoshaping sessions. Overall, DMS CB1R signaling inhibition blocked Pavlovian outcome devaluation. After extended training, male rats were sensitive to de
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
Well, it appears that USDA has finally taken more steps toward sharing more of the H5N1 cattle data. Really grateful to this research team for sharing this, though I hope they weren’t holding on to the data solely to ensure they published first. https://t.co/iHiLveGytp